Antimicrobial dosage in renal failure: a unifying nomogram.
A concise method is presented for calculating the dosage of commonly used anti-microbial agents in patients with impaired renal function.
Biomedical subjects
Publications and source records attributed to C S Bryan.
A concise method is presented for calculating the dosage of commonly used anti-microbial agents in patients with impaired renal function.
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Optimun therapy with carbenicillin entails the use of high serum concentrations and the risk of significant dose-related toxicity. We report a study of serum clearance method of dose adjustment of carbenicillin patients with normal and imparied renal function. This method was found to provide serum concentrations considered to be satisfactory in every instance, by either constant-rate or intermittent infusion, and should enable greater precision in the use of the antibiotic. Implications of these findings aimed at providing dosage schedules for patients with renal failure are discussed.
Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.
An immunochemical and functional analysis of the classical and alternate complement pathways in human serum was performed in the presence of 10 mM ethylene glycol tetraacetic acid (EGTA) and MgCl(2)-EGTA (MgEGTA), chelating agents which have been recently utilized as a means of distinguishing between these two complement pathways. Total hemolytic activity, integrity of the C1 complex, hemolytic activity of C2, conversion of factor B (C3 proactivator), and complement-dependent bactericidal activity were studied. The effect of these chelators on activation of complement pathways by Escherichia coli, by sensitized erythrocytes as a prototype of activators of the classical pathway, and by zymosan as a prototype of alternate (properdin) pathway activators was studied. Human serum containing 10 mM EGTA, which provides almost no ionized calcium and considerably less ionized magnesium than unchelated serum, allowed consumption of complement via the alternate (properdin) pathway, but blocked the classical pathway as judged by disintegration of the C1 complex and lack of utilization of C2. However, activity of the alternate complement pathway in EGTA serum, as judged by conversion of factor B and bactericidal activity against gram-negative bacteria, was distinctly suboptimal. Addition of magnesium ion in a concentration equimolar to EGTA (MgEGTA serum), while still providing conditions in which the C1 complex dissociated, significantly enhanced alternate complement pathway-mediated bactericidal activity. However, in MgEGTA serum considerable fluid-phase activation of the alternate pathway, as indicated by decrease in 50% hemolytic complement (CH(5 0)) titers and conversion of factor B to its active form in the absence of any activating challenge, was observed. Moreover, some fluid-phase consumption of C2 was observed in MgEGTA serum, even though, as mentioned, the C1 complex was shown to be dissociated under these conditions. MgEGTA-related activation of C2 and of the alternate (properdin) pathway of complement was significantly enhanced by the presence of zymosan and E. coli. These results indicate that use of the chelating agents EGTA and MgEGTA to differentiate between classical and alternate pathway activation of human complement is more complex than has hitherto been suggested. In EGTA serum, spontaneous activation of either pathway does not occur but bactericidal activity, as a measure of biologic function of complement, is suboptimal. In MgEGTA serum, bactericidal activity is fully expressed, but there is considerable instability, in terms of fluid-phase activation, in Mg(2+)-dependent components of both pathways. Thus, caution is indicated in the use and interpretation of the effects of these chelating agents on biologic functions mediated by either pathway of human complement.
Impairment of penicillin G excretion in renal failure may result in life-threatening, dose-related toxicity. We report a method for achieving a desired mean serum penicillin G concentration in patients with renal failure, with minimal risk of both undertreatment and drug toxicity. The method is based on the linear relation between the total plasma clearance of penicillin G (Cpen) and the endogenous creatinine clearance. The daily maintenance dose of penicillin G (units) is defined by the product, Cpen (ml/min) times desired mean serum penicillin G concentration (mug/ml) times 2300. Application of this method to patients with various degrees of renal impairment by either constant-rate infusion or intermittent infusion gave serum penicillin G concentrations within the desired range in all but 1 of 15 instances. On the basis of these observations, practical guidelines for "comparably massive" penicillin G therapy are suggested.
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One measure used in the management of staphylococcal disease outbreaks in newborn nurseries is to obtain nasal cultures from nursery personnel and then treat nasal carriers with topical antibiotic ointments. Because recent infection control guide-surveyed current practices in larger hospitals in the U.S.A. Seventy-one percent of respondents indicated that they would obtain nasal cultures from personnel during a staphylococcal disease outbreak, and 40% indicated that they would prescribe topical antibiotic ointments for personnel with positive nasal cultures before the results of bacteriophage typing became known. Because little has been written about the efficacy of topical intranasal antibiotics within the past decade, we compared bacitracin ointment with a vancomycin ointment for treatment of the staphylococcal nasal carrier state. Both ointments reduced nasal carriage in the majority of instances. However, similar reduction was also observed in an untreated control group. The need for different approaches to the problem of nasal carriers is discussed.
Prospective surveillance of 1,527 episodes of bacteremia in the four major hospitals serving a community of 300,000 revealed striking differences among the hospitals. The rate of community-acquired bacteremia ranged from 1.9 to 6.8 per 1000 discharges; the rate of nosocomial bacteremia ranged from 0.9 to 9.8 per 1000 discharges. Death rates attributed to nosocomial bacteremias varied among the hospitals by as much as 40-fold. Nosocomial bacteremias were less frequent at two community non-teaching hospitals than at two teaching hospitals. Although fewer blood cultures were obtained at the nonteaching hospitals, the ratio of blood cultures obtained to deaths attributed to bacteremic infection was highest at these hospitals, suggesting that physicians recognized the importance of obtaining blood cultures in critically ill patients. The potential usefulness of bacteremia surveillance is reviewed. It is suggested that hospitals serving a single community might constitute an appropriate unit for such surveillance.